Mutations in ZMYND10, a gene essential for proper axonemal assembly of inner and outer dynein arms in humans and flies, cause primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger resequencing in PCD-affected families afflicted with combined IDA and ODA defects, we found that 6/38 (16%) carried biallelic mutations in the conserved zinc-finger gene BLU (ZMYND10). ZMYND10 mutations conferred dynein-arm loss seen at the ultrastructural and immunofluorescence level and complete cilia immotility, except in hypomorphic p.

Effete, a Drosophila chromatin-associated ubiquitin-conjugating enzyme that affects telomeric and heterochromatic position effect variegation.

Drosophila telomeres are elongated by the transposition of telomere-specific retrotransposons rather than telomerase activity. Proximal to the terminal transposon array, Drosophila chromosomes contain several kilobases of a complex satellite DNA termed telomere-associated sequences (TASs). Reporter genes inserted into or next to the TAS are silenced through a mechanism called telomere position effect (TPE).

Forkhead transcription factor Fd3F cooperates with Rfx to regulate a gene expression program for mechanosensory cilia specialization.

Cilia have evolved hugely diverse structures and functions to participate in a wide variety of developmental and physiological processes. Ciliary specialization requires differences in gene expression, but few transcription factors are known to regulate this, and their molecular function is unclear. Here, we show that the Drosophila Forkhead box (Fox) gene, fd3F, is required for specialization of the mechanosensory cilium of chordotonal (Ch) neurons.

Linking specification to differentiation: From proneural genes to the regulation of ciliogenesis.

Much of developmental biology is concerned with the processes by which cells become committed to particular fates in a regulated fashion, whereas cell biology addresses, among other things, the variety of differentiated forms and functions that cells can acquire. One open question is how the regulators of the former process lead to attainment of the latter. 'High-level' regulators of cell fate specification include the proneural factors, which drive cells to commit as precursors in the sensory nervous system.

The gene regulatory cascade linking proneural specification with differentiation in Drosophila sensory neurons.

In neurogenesis, neural cell fate specification is generally triggered by proneural transcription factors. Whilst the role of proneural factors in fate specification is well studied, the link between neural specification and the cellular pathways that ultimately must be activated to construct specialised neurons is usually obscure. High-resolution temporal profiling of gene expression reveals the events downstream of atonal proneural gene function during the development of Drosophila chordotonal (mechanosensory) neurons.

The function and regulation of the bHLH gene, cato, in Drosophila neurogenesis.

Background: bHLH transcription factors play many roles in neural development. cousin of atonal (cato) encodes one such factor that is expressed widely in the developing sensory nervous system of Drosophila. However, nothing definitive was known of its function owing to the lack of specific mutations.

Multiple enhancers contribute to spatial but not temporal complexity in the expression of the proneural gene, amos.

Background: The regulation of proneural gene expression is an important aspect of neurogenesis. In the study of the Drosophila proneural genes, scute and atonal, several themes have emerged that contribute to our understanding of the mechanism of neurogenesis. First, spatial complexity in proneural expression results from regulation by arrays of enhancer elements.

EGF receptor signaling triggers recruitment of Drosophila sense organ precursors by stimulating proneural gene autoregulation.

In Drosophila, commitment of a cell to a sense organ precursor (SOP) fate requires bHLH proneural transcription factor upregulation, a process that depends in most cases on the interplay of proneural gene autoregulation and inhibitory Notch signaling. A subset of SOPs are selected by a recruitment pathway involving EGFR signaling to ectodermal cells expressing the proneural gene atonal. We show that EGFR signaling drives recruitment by directly facilitating atonal autoregulation.

The proneural proteins Atonal and Scute regulate neural target genes through different E-box binding sites.

For a particular functional family of basic helix-loop-helix (bHLH) transcription factors, there is ample evidence that different factors regulate different target genes but little idea of how these different target genes are distinguished. We investigated the contribution of DNA binding site differences to the specificities of two functionally related proneural bHLH transcription factors required for the genesis of Drosophila sense organ precursors (Atonal and Scute). We show that the proneural target gene, Bearded, is regulated by both Scute and Atonal via distinct E-box consensus binding sites.

The Drosophila proneural gene amos promotes olfactory sensillum formation and suppresses bristle formation.

Proneural genes encode basic-helix-loop-helix (bHLH) transcription factors required for neural precursor specification. Recently amos was identified as a new candidate Drosophila proneural gene related to atonal. Having isolated the first specific amos loss-of-function mutations, we show definitively that amos is required to specify the precursors of two classes of olfactory sensilla.